Chen Zhang1, Dong Qian2, Hongzhi Zhao3, Nan Lv4, Pei Yu5, Zhe Sun2. 1. Tianjin Medical University, Tianjin 300070, China; Department of Minimal Invasive Surgery, Tianjin Nankai Hospital, Tianjin 300100, China. 2. Department of Minimal Invasive Surgery, Tianjin Nankai Hospital, Tianjin 300100, China. 3. Department of Minimal Invasive Surgery, Tianjin Nankai Hospital, Tianjin 300100, China. Electronic address: zhaohongzhi_tnh@126.com. 4. Tianjin Institute of Medicine and Pharmaceutical Science, Tianjin, 300020, China. 5. Department of Endocrinology, Metabolic Disease Hospital, Tianjin Medical University,Tianjin 300070, China.
Abstract
OBJECTIVES: MicroRNAs (miRNAs) are involved in the pathological progression of various disease including type 2 diabetes (T2D). Chronic inflammation in adipose tissue is a cause of insulin resistance and T2D. MiR-17 palys an anti-inflammatory role in many biological processes. We hypothesized that miR-17 suppressed inflammatory macrophage that is related to insulin resistance in patients with T2D. METHODS: Macrophage migration and secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β were detected through transwell migration assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was tested by the radioactivity of tritium-labeled glucose in 3T3-L1 adipocytes. Dual luciferase reporter gene assay was employed to evaluate the interaction between miR-17 and 3'UTR of ASK1. RESULTS: Our results showed that miR-17 inhibited macrophage infiltration and secretion of TNF-α, IL-6 and IL-1β. Moreover, insulin-stimulated glucose uptake of 3T3-L1 was suppressed by treatment with LPS-induced macrophage conditioned media (CM), whereas the opposite effect was showed after treatment with the CM of macrophages transfected with miR-17. Furthermore, we found that miR-17 directly prevented expression of ASK1 by binding to its 3'UTR. CONCLUSION: miR-17 improved inflammation-induced insulin resistance by suppressing ASK1 expression in macrophages. These results indicated that miR-17 had an anti-diabetic acitivity by its anti-inflammation effect on macrophage.
OBJECTIVES: MicroRNAs (miRNAs) are involved in the pathological progression of various disease including type 2 diabetes (T2D). Chronic inflammation in adipose tissue is a cause of insulin resistance and T2D. MiR-17 palys an anti-inflammatory role in many biological processes. We hypothesized that miR-17 suppressed inflammatory macrophage that is related to insulin resistance in patients with T2D. METHODS: Macrophage migration and secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β were detected through transwell migration assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was tested by the radioactivity of tritium-labeled glucose in 3T3-L1 adipocytes. Dual luciferase reporter gene assay was employed to evaluate the interaction between miR-17 and 3'UTR of ASK1. RESULTS: Our results showed that miR-17 inhibited macrophage infiltration and secretion of TNF-α, IL-6 and IL-1β. Moreover, insulin-stimulated glucose uptake of 3T3-L1 was suppressed by treatment with LPS-induced macrophage conditioned media (CM), whereas the opposite effect was showed after treatment with the CM of macrophages transfected with miR-17. Furthermore, we found that miR-17 directly prevented expression of ASK1 by binding to its 3'UTR. CONCLUSION:miR-17 improved inflammation-induced insulin resistance by suppressing ASK1 expression in macrophages. These results indicated that miR-17 had an anti-diabetic acitivity by its anti-inflammation effect on macrophage.
Authors: F Ramzan; R F D'Souza; B R Durainayagam; A M Milan; N C Roy; M C Kruger; C J Henry; C J Mitchell; D Cameron-Smith Journal: Genes Nutr Date: 2020-02-04 Impact factor: 5.523
Authors: Seley Gharanei; Kiran Shabir; James E Brown; Martin O Weickert; Thomas M Barber; Ioannis Kyrou; Harpal S Randeva Journal: Cells Date: 2020-11-16 Impact factor: 6.600